Alzheimer's disease (AD) is a progressive degenerative disease of the brain primarily associated with aging. Prevalence of AD in the United States in 2000 was close to 4.5 Million. It was estimated that about one in ten individuals over 65 and nearly half of those over 85 are affected by Alzheimer's disease. Approximately 360,000 patients will be diagnosed with AD each year in the United States alone.
Clinical presentation of AD is characterized by loss of memory, cognition, reasoning, judgment, and orientation. As the disease progresses, motor, sensory, and linguistic abilities are also affected until there is global impairment of multiple cognitive functions. These cognitive losses occur gradually, but typically lead to severe impairment and eventual death in the range of four to twelve years.
Alzheimer's disease is characterized by two major pathologic observations in the brain: neurofibrillary tangles and beta amyloid plaques (neuritic plaques), comprised predominantly of an aggregate of a peptide fragment known as amyloid beta (Aβ). Individuals with AD exhibit characteristic beta-amyloid deposits in the brain (beta amyloid plaques) and in cerebral blood vessels (beta amyloid angiopathy) as well as neurofibrillary tangles. Neurofibrillary tangles occur not only in Alzheimer's disease but also in other dementia-inducing disorders. Both soluble oligomeric Aβ and fibrillar Aβ are also believed to be neurotoxic and inflammatory.
ALZ-801 (3-(2-amino-3-methylbutanamido)propane-1-sulfonic acid), a prodrug of 3-amino-1-propanesulfonic acid (3APS, Tramiprosate) is a promising investigational product candidate for the treatment of Alzheimer's disease. Tramiprosate is believed to act by reducing the deposition and/or load of amyloid in the brain through its binding to soluble Aβ peptide.
There remains a need for additional and improved pharmaceutical agents for preventing and treating amyloid-related diseases such as Alzheimer's disease. For improved pharmaceutical agents, it is desirable to increase the agent's bioavailability, stability and/or blood brain barrier crossing. These, and other needs, can be satisfied by the disclosure herein of new compositions and uses thereof to treat various medical disorders.